Studies on individuals with severe genetic defects in serotonin function can shed light on the role of this neurotransmitter in behavior and on the role of milder functional variants in serotonin genes in predisposing individuals to psychopathologies and to alcoholism. We have targeted for these studies patients with a positive family history or significant dysmorphology with severe mental retardation, pervasive developmental disorder, infantile autism, obsessive compulsive disorder, disruptive behavioral disorder or other disrupted behaviors which are presumptively under serotonergic influence. We are identifying probands for family studies by measuring the serotonin metabolite 5HIAA in cerebrospinal fluid. Probands and family members receive a detailed neurologic and psychiatric assessment and familial transmission and comorbidity is concurrently assessed. Subjects with aberrant serotonin function and their families will be the focus for genetic linkage analyses using dispersed probes and direct studies (for example sequencing) of candidate genes such as tryptophan hydroxylase.